@article{3f8d3a5036da418ca83239ea45304554,
title = "COVID-19 vaccination elicits an evolving, cross-reactive antibody response to epitopes conserved with endemic coronavirus spike proteins",
abstract = "The COVID-19 pandemic has triggered the first widespread vaccination campaign against a coronavirus. Many vaccinated subjects are previously naive to SARS-CoV-2; however, almost all have previously encountered other coronaviruses (CoVs), and the role of this immunity in shaping the vaccine response remains uncharacterized. Here, we use longitudinal samples and highly multiplexed serology to identify mRNA-1273 vaccine-induced antibody responses against a range of CoV Spike epitopes, in both phylogenetically conserved and non-conserved regions. Whereas reactivity to SARS-CoV-2 epitopes shows a delayed but progressive increase following vaccination, we observe distinct kinetics for the endemic CoV homologs at conserved sites in Spike S2: these become detectable sooner and decay at later time points. Using homolog-specific antibody depletion and alanine-substitution experiments, we show that these distinct trajectories reflect an evolving cross-reactive response that can distinguish rare, polymorphic residues within these epitopes. Our results reveal mechanisms for the formation of antibodies with broad reactivity against CoVs.",
keywords = "CP: Immunology, CP: Microbiology, SARS-CoV-2, multiplexed serology, vaccination",
author = "Elko, {Evan A.} and Nelson, {Georgia A.} and Mead, {Heather L.} and Kelley, {Erin J.} and Carvalho, {Sophia T.} and Sarbo, {Nathan G.} and Harms, {Caroline E.} and {Le Verche}, Virginia and Cardoso, {Angelo A.} and Ely, {Jennifer L.} and Boyle, {Annalee S.} and Alejandra Pi{\~n}a and Henson, {Sierra N.} and Fatima Rahee and Keim, {Paul S.} and Celona, {Kimberly R.} and Jinhee Yi and Settles, {Erik W.} and Bota, {Daniela A.} and Yu, {George C.} and Morris, {Sheldon R.} and Zaia, {John A.} and Ladner, {Jason T.} and Altin, {John A.}",
note = "Funding Information: We are grateful to all vaccinated and convalescent blood donors, to Carmel Plude for phlebotomy, to Danielle Metz and Bethine Moore for clinical research coordination, and to Haley Nunnallay for technical assistance in generating the MagPix data. This work was supported by the NIAID ( U24AI152172 , U24AI152172-01S1 , U24AI152172-IOF , PI: J.A.A.), the California Institute for Regenerative Medicine ( CLIN2COVID19-11775 , PI: J.A.Z), the State of Arizona Technology and Research Initiative Fund (TRIF, administered by the Arizona Board of Regents, through Northern Arizona University ), the Flinn Foundation , and The Cowden Endowment for Microbiology . The contents of this publication are solely the responsibility of the authors and do not necessarily represent the official views of CIRM or any other agency of the State of California. Publisher Copyright: {\textcopyright} 2022 The Author(s)",
year = "2022",
month = jul,
day = "5",
doi = "10.1016/j.celrep.2022.111022",
language = "English (US)",
volume = "40",
journal = "Cell Reports",
issn = "2211-1247",
publisher = "Cell Press",
number = "1",
}